Since the discovery of norfloxacin, synthetic quinolone antibacterial agents have been significantly improved in terms of antibacterial activity and pharmacokinetics, and these agents have evolved into chemotherapeutic agents useful for treatment of systemic infectious diseases. Many of such synthetic quinolone compounds are currently used in clinical field.
In recent years, bacteria less susceptible to synthetic quinolone antibacterial agents have come to be increasingly developed in clinical field. For example, among Gram-positive bacteria, MRSA (methicillin-resistant Staphylococcus Aureus) and PRSP (penicillin-resistant Streptococcus Pneumoniae) in susceptible to β-lactam antibiotics, and VRE (vancomycin-resistant Enterococcus) in susceptible to an aminoglycoside antibacterial agent, a number of new types of bacteria that are resistant to drugs other than synthetic quinolone antibacterial agents and have low susceptibility to synthetic quinolone antibacterial agents is increasing. Therefore, there has been urgent need for development of a drug having higher efficacy in clinical field.
Apart from the above, it has become apparent that such synthetic antibacterial agents have various side effects such as convulsion which could occur when used in combination with a non-steroidal anti-inflammatory agent and phototoxicity. Therefore, development of a safer synthetic quinolone antibacterial agent is keenly demanded.
It has been known that antibacterial activity, pharmacokinetics, and safety of a synthetic quinolone antibacterial agent are influenced in large part with the structure of a substituent at the 7- or 1-position of the quinolone skeleton. Quinolone derivatives in which the 7-position of the quinolone skeleton is substituted by a 3-aminomethylpyrrolidinyl group are known to exhibit strong antibacterial activity on Gram-positive and Gram-negative bacteria. One example is a 7-[3-(1-aminomethyl)pyrrolidin-1-yl]quinolonecarboxylic acid derivative (see Non-Patent Document 1). Moreover, examples of quinolonecarboxylic acid derivatives derived from this specific quinolonecarboxylic acid derivative through substitution of the aminomethyl group include a 7-[3-(1-aminoethyl)pyrrolidin-1-yl]quinolonecarboxylic acid derivative (see Non-Patent Document 2), a 7-[3-(1-amino-1-methylethyl)pyrrolidin-1-yl]quinolonecarboxylic acid derivative (see Non-Patent Document 3), and a 7-[3-(1-aminoalkyl)pyrrolidin-1-yl]quinolonecarboxylic acid derivative (see Non-Patent Document 4).
However, most of the above-mentioned quinolonecarboxylic acid derivatives affect not only on bacteria but also on eukaryotic cells, because of low selective toxicity (see Non-Patent Document 5). Therefore, it is difficult for these derivatives to be used as pharmaceutical drugs or veterinary drugs. In fact, none of them have actually been used in clinical field so far.
Meanwhile, there are known quinolonecarboxylic derivatives related to the present invention such as compound (A) (see Patent Document 1) and compound (B) (see Patent Document 2) in which the 7-position of the quinolone skeleton is substituted by a 3-(1-aminocycloalkyl)pyrrolidinyl group. Note that the definitions of various substituents in compounds (A) (or (B)) are given in Patent Document 1 (or 2), and are not pertinent to the definitions provided in the present specification, even in cases where symbols are in common.

However, all the quinolonecarboxylic derivatives specifically disclosed in the above-mentioned applications have a common feature that the 8-position on the quinolone skeleton is substituted by a methyl group or a methoxy group, or that a methoxy group forms a ring with the nitrogen atom on the quinolone structure. These compounds exhibit relatively strong antibacterial activities as compared with conventional quinolone derivatives. However, they have strong acute toxicity and test positive in a micronucleus test, which is an indicative test for genetic toxicity.
Another known type of quinolonecarboxylic derivatives are quinolonecarboxylic derivatives (C) in which the 7- and 8-positions is substituted by a 3-(1-aminocycloalkyl)pyrrolidinyl group and a cyano group, respectively, and the 6-position is substituted only by a hydrogen atom (see Patent Document 3). Note that the definitions of various substituents in compound (C) are given in Patent Document 3, and such definitions are not pertinent to the definitions provided in the present specification, even in cases where symbols are in common.

Furthermore, there are other quinolonecarboxylic derivatives disclosed so far, in which the 8- and 6-positions are substituted by a cyano group and a fluorine atom, respectively (see Patent Documents 4 to 8). However, compounds of this type do not have a 3-(1-aminocycloalkyl)pyrrolidinyl group at the 7-position.    Patent Document 1: International Publication WO 96/00208 pamphlet    Patent Document 2: International Publication WO 97/19072 pamphlet    Patent Document 3: International Publication WO 02/40478 pamphlet    Patent Document 4: European Patent No. 235762 specification    Patent Document 5: West Germany Patent No. 3702393 specification    Patent Document 6: International Publication WO 96/11194 pamphlet    Patent Document 7: International Publication WO 97/31001 pamphlet    Patent Document 8: International Publication WO 98/26779 pamphlet    Non-Patent Document 1: Journal of Medical Chemistry, Vol. 29, p. 445 (1986)    Non-Patent Document 2: Journal of Medical Chemistry, Vol. 36, p. 871 (1993)    Non-Patent Document 3: Journal of Medical Chemistry, Vol. 37, p. 733 (1994)    Non-Patent Document 4: Chemical & Pharmaceutical Bulletin, Vol. 42, p. 1442 (1994)